Published in Regulatory Toxicology and Pharmacology, researchers from the trade association Cosmetics Europe, consultancies, a university, and several major beauty brands – Beiersdorf, L’Oréal Research & Innovation, Procter & Gamble, and Unilever’s Safety & Environmental Assurance Centre – outlined the new approach for cosmetic toxicology assessment.
The 10-step framework combined read-across (RAX) assessment approaches and new approach methodologies (NAMs) in biology and kinetics, such as in vitro assays, toxicogenomics and metabolomics. It had been designed for use in cases where a threshold of toxicological concern (TTC) approach was not possible for cosmetics safety assessment. The research had been funded under Cosmetics Europe’s Long Range Science Strategy (LRSS) programme; designed to spearhead advances in ongoing research projects such as like its Alternative Approaches to Animal Testing (AAT) project.
‘Exposure-driven’ and ‘evidence-based’ approach
The team said the work “built on” well-established approaches, including evaluation methods outlined under the EU animal-free testing consortium SEURAT-1 programme using an exposure-based mode of action (MoA) driven workflow without generating animal data and integrated strategies detailed by the International Cooperation on Cosmetics Regulation (ICCR).
“Our 10-step read-across (RAX) framework builds on established approaches for defining chemical similarity by substantiating hypotheses on toxicological similarity of substances using NAM in both the biological and kinetic domains,” the researchers wrote.
“…We propose a tiered exposure-driven and evidence-based approach to read-across, where new approach methodologies are used to strengthen a mode/mechanism of action hypothesis and support data on kinetics and exposure.”
The researchers said that following the framework enabled a next generation risk assessment (NGRA) to be performed “with an acceptable level of confidence” for a “data-poor target substance” – one that had no or inadequate safety data. It also benefited from being a “flexible and iterative procedure”, they said. “…The possibilities for using different types of evidence depending on the problem formulation, leads to an approach based on good science but one that is by nature less prescriptive and more flexible.”
The researchers presented two case studies as part of the study to illustrate how the framework could be followed in practice but said further investigation would be required, as well as regulatory dossiers on full read-across submissions to “help cement” wider use and understanding. Additional studies would also help determine which kinds of data were most helpful for supporting read-across strategies, they said.
Read-across an ‘important stepping stone’ to animal-free future
Whilst animals, largely mice, remained extensively used for medical research and testing worldwide, the EU had implemented a ban on all animal testing for cosmetic products and cosmetic ingredients under its Cosmetics Regulation 1223/2009 in 2013. The move followed an initial ban on testing for certain endpoints in finished products in 2004 and ingredients in 2009. The European Parliament’s goal was to reach a blanket global ban on animal testing in cosmetics by 2023 – widely supported by the beauty and personal care industry.
“It is a long-term ambition of the cosmetics sector to derive an approach that relies on no animal data what so ever,” the study researchers wrote.
But for this to be achieved, they said there had to be “confidence in NAMs to cover the breadth and depth of the known world of mechanistic toxicology” – the knowledge of which could then be implemented to analyse human adverse outcome pathways or human safety.
Read-across (RAX) methods were considered an “important stepping stone in this journey” and “particularly pertinent where animal testing, for systemic toxicology and kinetics, is not legally possible”. However, in practice, positioning RAX into regulatory decision-making for human safety had been challenging – a hurdle the 10-step framework aimed to overturn.
In June, last year, Cosmetics Europe unveiled its New Science Programme - a five-year, industry-led initiative designed to drive and shape future uptake and regulatory acceptance of non-animal testing alternatives in cosmetics.
Source: Regulatory Toxicology and Pharmacology
Published online ahead of print, doi: 10.1016/j.yrtph.2021.105094
Title: “A 10-step framework for use of read-across (RAX) in next generation risk assessment (NGRA) for cosmetics safety assessment”
Authors: C. Alexander-White et al.